II. Turning the Oxygen Dial as a Therapy

Introduction: We recently demonstrated that chronically lowering inhaled oxygen tensions can extend the life of a mitochondrial disease mouse model by five-fold. Moreover, starting late-stage disease treatment can not only prevent, but even reverse the disease. MRI-detectable lesions are completely cured within weeks of breathing chronic hypoxia. This work has already led to a phase 1 clinical trial for healthy human hypoxia exposure. We believe that this paradoxical finding is just the tip of the iceberg. While small molecules and biologics are the most common forms of therapy, we believe we have uncovered a new mode of treating metabolic disorders. We now hope to extend our findings to additional inborn errors of metabolism, as well as more common metabolic disorders.

Approaches: We use a combination of cardiorespiratory physiology, energy metabolism (e.g. oxygen consumption, body composition, etc.) and in-vivo tracer studies to study how modifying oxygen levels can treat diseases.

Biomedical Relevance: We hope to develop therapies for additional inborn errors of metabolism and common conditions by turning the “oxygen dial” to low or high oxygen.